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Pharmacology - Year 2 > Insulin & Hypoglycaemics > Flashcards

Insulin & Hypoglycaemics Flashcards

1
Q

What Does Insulin Do?

A 
Increase Glucose Uptake, Storage & Utilization 
Increase Protein Synthesis
Increase Triglyceride Synthesis
Increase Gene Expression & Growth
Decrease Proteolysis
Decrease Lipolysis and Lipid Oxidation
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2
Q

What is the Mode of Action of Insulin?

A
  1. Receptor Activation
  2. Signal Transduction
  3. Signalling Cascades Mediated by IRS2
  4. Functional Effects
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3
Q

What are the objectives of diabetes treatment?

A

Achieve normoglycaemia
Return blood pressure & cholesterol levels to normal
Adopt a healthy lifestyle to protect against long-term complications.

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4
Q

Broad Treatment plans of T1DM

A

lifelong insulin, healthydiet, regular exercise

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5
Q

Broad Treatment plans of T2DM

A 
Lifestyle changes (diet, weight, activity). 
Hypoglycaemic therapy and/or insulin.
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6
Q

Name short duration and rapid onset insulin therapy?

A

insulin aspart, insulin glulisine, insulin lispro
Given sc or iv
onset = 30-60mins
peak action - 2-4hours
Injected just before, with or just after food and only lasts long enough for the meal at which it is are taken.

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7
Q

Name Intermediate / Longer Duration onset insulin therapy?

A 
Insulin detemir
insulin glargine
insulin zinc suspension
isophane insulin
protamine zinc insulin
Onset = 1-2hours 
Peak = 4-12houes
Duration = 16-35hours
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8
Q

Biphasic Insulin Preparations

A

Mixture of intermediate & fast acting
Rapid onset
Long-lasting actions

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9
Q

Glucagon Therapy

A

Taken to promote =

  1. Glycogenolysis (glycogen to glucose)
  2. Gluconeogenesis
  3. Lipolysis (fat to FAs)

First-aid treatment for severe hypoglycaemia when oral glucose is not possible or desired

Route: injection; intramuscular, intravenous or subcutaneous

Must be reconstituted prior to use

Acutely raises plasma glucose levels

Common side-effects include headache and nausea

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10
Q

T2DM Therapies Secretagogues I - all end in IDE

A

Two types, noth thave the same action = boost insulin release; enhance the normal physiology of glucose-stimulated insulin secretion. Antagonists of Katp channel

Sulphonylureas

Meglitinides

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11
Q

Sulphonylureas

A

Small molecule antagonists of the KATP Channel
Taken oral, twice daily, pre meal usually combined with other therapies
Short Lasting Formulations: gliclazide (Diamicron); tolbutamide (Orinase)
Long-Lasting Formulations: chlorpropamide (Diabinese); glibenclamide; glipizide (Glucotrol); glimepiride (Amaryl)

side effects = hypoglycaemia

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12
Q

Meglitinides

A

Small molecule antagonists of the KATP Channel

Oral agents: Once or twice daily with or shortly before a meal

Short Acting = Repaglinide (Prandin®) and Nateglinide (Starlix®)

May have a decreased the risk of hypoglycaemia compared to SUs, particularly the elderly

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13
Q

Incretin Mimetics are Secretagogues That Have a Different Mode of Action! Why?

A

GLP-1 cannot be used as it has a very short half-life and is rapidly broken down by the endogenous enzyme dipeptydylpeptidase-4 (DPP-4)

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14
Q

How do Incretin Mimetic work? Background?

A

Boost insulin release by enhancing the normal physiology of incretin-mediated insulin secretion.

Peptide-Agonists of the GLP-1 Receptor and not broken down by dipeptydylpeptidase-4 (DPP-4)

Injectable agents, s.c.

Combined with other therapies

Much reduced risk of hypoglycaemia compared to sulphonylureas

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15
Q

Byetta

A

Secretagogues II
Exenatide and Liraglutide

Injection

Side effects = gastro-intestinal disturbances including nausea, vomiting, diarrhoea, dyspepsia, abdominal pain and distension, gastro-oesophageal reflux disease, decreased appetite; headache, dizziness, agitation, asthenia; increased sweating, injection-site reactions; antibody formation

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16
Q

Gliptins

A

Incretin Mimetic

Boost insulin release by enhancing the normal physiology of incretin-mediated insulin secretion.

Inhibitors of dipeptydylpeptidase-4 (DPP-4); raises the half-life of serum GLP-1

Tablet – Oral

Can be combined with other medications; novel formulations e.g. Eucreas®, Janume® - gliptins+metformin

Side-effects vomiting, dyspepsia, gastritis; peripheral oedema; headache, dizziness, fatigue; upper respiratory tract infection, urinary tract infection, gastroenteritis, sinusitis, nasopharyngitis; hypoglycaemia, myalgia; less commonly dyslipidaemia, hypertriglyceridaemia, erectile dysfunction, arthralgia; also reported rash

17
Q

Diazoxide

A

To treat congenital hyperinsulinism in infancy, insulinomas, severes cases of transient hypoglycaemia
Small molecule agonist of the Katp channel

Side effects =
anorexia, nausea, vomiting, hyperuricaemia,
hypotension, oedema, tachycardia, arrhythmias,
extrapyramidal effects; hypertrichosis on prolonged treatment

18
Q

Insulin Sensitizers

A

Insulin Sensitizers improve the sensitivity of target organs to insulin

There are two types =

  1. Biguanides = activating enzymes
  2. Thiazolidinediones = modifying the transcription of genes
19
Q

The Mode of Action of Biguanides?

A
  1. Receptor Activation
  2. Signal Transduction
  3. Signalling Cascades Mediated by IRS2
  4. Agonist of AMP-activated protein kinase (AMPK)

Function effects =
Increase Glucose Uptake, Storage & Utilization, Protein Synthesis, Triglyceride Synthesis, Gene Expression & Growth
Decrease Proteolysis, Lipolysis and Lipid Oxidation

Basically prevents hepatic production of glucose, overcomes insulin resistance by improving insulin sensitivity

20
Q

Metformin

A

Combinational Therapies

  • pioglitazone (Actoplus Met)
  • glipizide (Metaglip)
  • glibenclamide (Glucovance),
  • sitagliptin (Janumet),
  • repaglinide (PrandiMet)
21
Q

Thiazolidinediones / glitazones

A

Activate PPARγ, a regulatory protein involved in the transcription of insulin-sensitive genes which regulate glucose and fat metabolism

Target adipocytes

Oral - 1/2 daily

Rosiglitizone - can also be combined with metformin or
glimepiride

22
Q

α-Glucosidase Inhibitors

A

Aim = Modifying Glucose Breakdown
Example = Acarbose
Action =
1. α-glucosidase converts oligosaccharides to glucose
2. Acarbose stops emzyme
3. slows absorb of fat foods
4. In patients, this provides a closer alignment of [impaired] insulin output with glucose uptake

Side effects = Flatulence, diarrhoea, abdominal pain, nausea, vomiting, indigestion, liver function problems, oedema, blood disorders, allergic skin reaction, intestinal problems.

23
Q

SGLT2 Inhibitors - end in ZIN

A 
Aim = Enhancing Glucose Release
Examples = Dapagliflozin*, canagliflozin, empagliflozin

SGLT2 inhibitors cause excess glucose to be eliminated in the urine; reducing hyperglycaemia

Potential Advantages: weight loss, insulin independent, low risk of hypoglycaemia, osmotic diuresis reduces hypertension

Pharmacology - Year 2 (6 decks)

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